This research will investigate the role that environmental magnetic fields (MF) play as an exogenous risk factor in the etiology of breast cancer. A plausible link between MFs and breast cancer is melatonin and Tamoxifen (see below) since both exert oncostatic action on human breast cancer cells in vitro. Recently we directly tested this hypothesis at the cellular level. We reported the first experimental evidence that a 12 mGauss, 60 Hz magnetic field blocks melatonin's (1O-9M) natural growth inhibition of estrogen-positive MCF-7 human breast-cancer cells in vitro. Extending these studies to Tamoxifen (TAX)(10-7M), the drug of choice for management of breast cancer recurrence, we show that the cytostatic action of TAX on MCF- 7 cells is significantly inhibited by the same environmental MFs which suggests estrogen receptor (ER) involvement Thus, 12 mGauss environmental level magnetic fields which are frequently encountered in the home and workplace have the potential to significantly influence hormone and drug interactions with proliferating human breast cancer cells. We propose to investigate this MF interaction at the cellular level and to test several plausible mechanisms of action. In biophysical studies we will determine (a) the dose-threshold for the magnetic field strength, (b)the role of the magnetic vs. induced electric field, (c) frequency-dependence, (d) exposure-time dependence, and (e) reversibility of the MF blocking effect. A biological basis for the field interaction will be investigated in several important ways. it is possible that MFs may directly alter entry and/or distribution of MLT and TAX in MCF-7 cells, and immunohistologicaI studies will assess this interaction. Alternatively it is possible that MFs may influence estrogen receptor expression which could explain MF inhibition of TAX action, and possibly MLT action, and this will be assessed. MFs are reported to trigger early signal transduction events such as [Ca+2]i and it is possible that calcium signaling in exposed MCF-7 cells could overcome growth inhibition by MLT and TAX. We will follow changes in [Ca+2]i at the single-cell level using quantitative digital imaging microscopy. The above studies should significantly carify how environmental MFs influence hormone/drug regulation of proliferating human breast cancer cells.